Aggressive Clinical Trial Patient at JH

[London441]

Hi,

I’m happy to have found this network. I’m in a clinical trial at Johns Hopkins. My treatment course is more aggressive than standard and beyond obviously hoping it eradicates my cancer, It should do a tiny bit to shed more light on the efficacy of early aggressive multi modal treatment after RP in locally advanced men.

I was diagnosed in February 2019. 63 YO, first and only (I know!) PSA 15. MRI guided biopsy showed a lesion, predominantly Gleason 4+3 and a few 3+4 adenocarcinoma. Tumor was about half the size of the prostate with several 80% cores. ECE, SV invasion.

RP in June 2019. Negative margins, 1 lymph node out of 12 positive. PSA undetectable and remains so thus far. Nerves spared for what it’s worth.

Began clinical trial in September 2019 as follows:

Lupron (scheduled to be ongoing for 2 years unless guidelines change)

4 cycles of docetaxel chemo in November

2 months Zytiga 1000mg/day w prednisone 5 mg November-December

37 IMRT radiation treatments to pelvis and prostate bed completed last week

I know now, as all of us do in similar situations, is wait and see. We hope the creek, uh the PSA doesn’t rise. I suppose for many of us the truer measure comes when we get off ADT.

I credit my reasonable spiritual condition, work I love, wife, friends, medical care and attention to exercise and diet to having had a positive outlook and minimal side effects (other than lingering incontinence and total ED/no libido) from any of this so far. The ED would obviously be more of a concern if I didn’t believe function would return. I do, though I know it won’t be the same.

My question is simply this: Has anyone been in a similar trial or known anyone who has? I’m itching to get off the Lupron like anyone else, and wonder why 2 years. Does it really continue to work for that long? I’d hate to think all this is, essentially, simply thrown at guys who are deemed to be able to tolerate it well.

I know my treatment has been standard for my pathology with the exception of the Taxotere and Zytiga being added as part of adjunctive therapy. Naturally the hope is that it makes a difference if needed. Any experience most welcome thank you.

[Hidden]

Three recent concurrent studies in Europe have shown that adjuvant RT plus/minus ADT is NOT better (can be worse in overall survival) than early salvage RT. Consequently, the past dogma started gradually collapsing. Your trial is targeted at recuperating such a ground loss by betting "all in", i.e. by adding chemotherapy and using ADT to the extremes. It is an interesting subject for anyone watching from a safe distance. I am in a similar stage as you and can frankly tell you that I wouldn't participated in such a trial even if paid for this most handsomely. Yet, you are definitely doing a good deed to society. I will give that.

[London441 in reply to Hidden]

Thanks for your reply. I’ve seen the results of RADICALS, RAVES and GETUG AFU 17, if these are what you’re referring to. I note the assertion of little difference in salvage vs adjuvant RT, and indeed maybe there isn’t much. Certainly I wouldn’t use the words ‘have shown’ outright, and it seems to me that overall survival is generally a lot more about comorbidities exacerbated by long term ADT than radiation at any stage.

Your assertion that the addition of ADT and chemotherapy (you didn’t mention the abiraterone) is a direct reactionary response to ‘past dogma collapsing’ seems dubious and devoid of proof, never mind the question of whether the addition and timing of these agents actually assists or not.

Well this is what you get when you join a Internet forum. You may be absolutely right. And you might not be.

[Hidden in reply to London441]

It comes down to a cost/reward estimation after each one's own case. There is no universal truth, that's for sure. Keep us posted.

[timotur in reply to Hidden]

Agree with your thoughts jf. Similar pathology here as well. MO pushed scorched-earth tx with docetaxel + Zytiga adjuvant to radiation, but I turned it down, and PSA went to zero (<0.01) anyway on Lupron only after Brachy + IMRT. My thought was, what if the radiation tx actually worked? -- I would have been treating something that's not there.

Lupron/ADT SoC was initially 36 months, until a European study found 18 months gave similar results. So I'm shooting for 18-24 months and tapering off with 1 month shots every 6 weeks for the last six months.

[Hidden in reply to timotur]

Nice plan, especially the part regarding tapering off. The medical world had found the charms of the binary 0/1 environment long before George Boole. en.wikipedia.org/wiki/Boole...

They set a nice round number as the 0/1 slicing value, like 36, 24 or 18 months and let simplicity take it from there. One day, during some future century, they might find the usefulness of a servo system, i.e. give as much drive as the load demands and constantly re-adjust.

"Centrifugal governors were invented by Christiaan Huygens and used to regulate the distance and pressure between millstones in windmills in the 17th century. In 1788, James Watt adapted one to control his steam engine where it regulates the admission of steam into the cylinder(s), a development that proved so important he is sometimes called the inventor."

en.wikipedia.org/wiki/Centr...

[timotur in reply to Hidden]

jf: I had the same thoughts after reading about "adaptive dosing", an evolution-based strategy where therapy is halted before all of the hormone-sensitive cells are eliminated. Paraphrasing-- by killing most, but not all hormone-sensitive cells, they out-compete the castration-resistant cells and evolves the tumor back to the pre-treatment state. The resistant cells increase slightly with each cycle so that this treatment eventually fails. However, mathematical models demonstrate control may be durably maintained for up to 20 cycles - significantly longer than continuous therapy.

nature.com/articles/s41467-...

So the goal is the minimum level of Lupron to turn the AR signaling off (in binary terms, say a 1 is to grow, a 0 is not to grow). The minimum level of Lupron required to signal a zero, would allow increased time to resistance. This is like in digital communications, at the minimum-discernible-signal (MDS), you still get a perfect signal.

[Hidden in reply to timotur]

Nicely put. 73

[timotur in reply to Hidden]

hihi, 73 OM

[Hidden in reply to timotur]

QSL via healthunlocked.com

[Tall_Allen]

I've known a few men who had adjuvant Lupron+Zytiga with their adjuvant/salvage RT, no one who's had adjuvant docetaxel. The adjuvant ADT is lengthy because of your positive lymph node. 2-3 years is SOC in that situation. The hope is that the cancer is still constrained within the pelvic area, owing to the slow movement of lymph. You can read about the success of salvage whole pelvic RT + long term ADT here:

pcnrv.blogspot.com/2017/12/...

Hopefully, adding the chemo and the Zytiga will increase the odds of this therapy working. Thanks for participating in this clinical trial.

Are you doing penile rehab? Very hard to do with no libido.

[London441 in reply to Tall_Allen]

Thanks TA you are ubiquitous on here, very impressive. I hope you’re feeling better.

I don’t think it’s that the penile rehab is hard to do as much as it’s hard to WANT to do...sex is totally conceptual right now obviously.

Gotta get busy on it I know. My function was very good before surgery and was about 60% back but then came the Lupron and that was that. Penile rehab feels about as enticing as kegels but the analogy is apt-don’t feel like it, must do it anyway.

I wish my diligence in this area was similar to my workout habits which are stellar, although I say so myself.

[CalBear74]

I will soon have my eighth anniversary on Lupron. There are no hard and fast rules on time to resistance. For the first three years it was a combo therapy: Lupron and casodex, but my new urologist urged me to drop the Casodex.

[tallguy2]

Thanks for participating in this important study.

My journey has been sequential over the past 8 years, with all but one year being on ADT. I add the my chemo was done a bit earlier than SOC because I caught enlarged lymph nodes on an MRI for a back issue.

My journey: RP, salvage radiation, ADT, chemo, more EBRT, Provenge, and now a clinical trial with the combo of abiraterone and apalutamide. At each step the beast returned via increasing PSA and/or scans. Scans next month will provide first visual evidence of how this trial is treating me, but one month in PSA dropped from 2.2 to 0.7.

With Gleason 9 disease this sequence is, unfortunately, what most of us can expect unless a trial like yours shows efficacy.